Release Date:  June 6, 2001

RFA:  RFA-HL-01-006

National Heart, Lung, and Blood Institute
National Institute of Mental Health
National Institute of Nursing Research
National Institute of Child Health and Human Development

Letter of Intent Receipt Date:  September 20, 2001
Application Receipt Date:       October 16, 2001



The purpose of this initiative is to improve our understanding of fundamental 
biological mechanisms through which sleep deprivation and sleep disorders 
affect the cardiopulmonary, hematological, immunological, mental, and 
behavioral health of children.  Specific objectives are to advance our 
understanding of age-specific and individual requirements for sleep in 
children; define pathophysiological mechanisms underlying the emergence and 
progression of childhood sleep disorders; and identify genetic factors and 
phenotypic variations in sleep characteristics that determine childhood 
patterns of sleep and circadian rhythmicity.  Basic and clinical research is 
needed to provide a better understanding of the inter-relationship between 
sleep and other physiological systems.  Although sleep and sleep disturbances 
are important to health throughout childhood, the major focus of this RFA is 
on school-age children 4 to 18 years old.


The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of "Healthy People 2010," a PHS-led national 
activity for setting priority areas. This Request for Applications (RFA), 
Sleep and Sleep Disorders in Children, is related to one or more of the 
priority areas. Potential applicants may obtain a copy of "Healthy People 
2010" at


Applications may be submitted by domestic and foreign, for-profit and 
non-profit organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and eligible 
agencies of the Federal government.  Racial/ethnic minority individuals, 
women, and persons with disabilities are encouraged to apply as Principal 


This RFA will use the National Institutes of Health (NIH) R01 award mechanism. 
Responsibility for the planning, direction, and execution of the proposed 
project will be solely that of the applicant. The total project period for an 
application submitted in response to this RFA may not exceed four years. This 
RFA is a one-time solicitation. Future unsolicited competing continuation 
applications will compete with all investigator-initiated applications and be 
reviewed according to the customary peer review procedures. Awards will be 
made and managed by the National Heart, Lung, and Blood Institute (NHLBI) 
and/or National Institute of Child Health and Human Development (NICHD) and/or 
the National Institute of Mental Health (NIMH) and/or the National Institute 
for Nursing Research  (NINR).  Policies that govern the research grant 
programs of the NIH will prevail.  The anticipated award date is July1, 2002.

Specific application instructions have been modified to reflect "MODULAR 
GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH. 
Complete and detailed instructions and information on Modular Grant 
applications can be found at


The NHLBI intends to commit $3.1 million, the NICHD intends to commit 
$375,000, the NIMH intends to commit $375,000, and the NINR intends to commit 
$375,000 in total costs during fiscal year 2002 to fund eight to ten new  
grants in response to this RFA. An applicant may request a project period of 
up to four years and a budget for direct costs of up to $250,000 per year (10 
modules).  Because the nature and scope of the research proposed may vary, it 
is anticipated that the size of each award will also vary. Although the 
financial plans of the NHLBI, NICHD, NIMH, and NINR provide support for this 
program, awards pursuant to this RFA are contingent upon the availability of 
funds and the receipt of a sufficient number of meritorious applications.



Sleep is widely recognized as an essential biological function, but the 
mechanisms through which sleep influences overall health, and the significance 
of sleep disorders at different stages of childhood development are not well 
understood.   Sleep difficulties in young children are among the most common 
behavioral disturbances that families bring to the attention of pediatricians. 
Sleep disorders and sleep deprivation impair performance in school and 
diminish physical and mental health.  Many children complain about feeling 
tired during the day.  An estimated 20 to 30 percent of school-age children 
experiences some type of sleep disturbance and 15 percent report falling 
asleep during school.  There is concern that children may be particularly 
vulnerable to abnormalities resulting from sleep disturbances that may 
contribute to subsequent morbidity and mortality risks and potentially 
significant dysfunction as adults.   

Sleep disturbances are associated with altered immune responsiveness and with 
hormonal abnormalities that reduce resilience to stress and the ability to 
regulate blood sugar.  Disturbed sleep can also impair physical growth and 
sexual maturation by impeding the normal nocturnal secretion of growth 
hormone, and gonadotropins.  Animal studies indicate that sleep deprivation 
alters the pattern of gene expression in the brain and accelerates the loss of 
brain cells.   However, little is known about the impact of sleep deprivation 
on childhood development and its potential consequences on health.

Certain sleep disorders such as narcolepsy emerge by adolescence and persist 
into adulthood.  On average 14 years elapse between the onset of narcoleptic 
symptoms and correct diagnosis.  Failing to recognize the condition may lead 
to mislabeling a child as having learning disabilities or mood disorders 
increasing the risk of impaired personal and professional development.   Sleep 
apnea affects 1-3% of children and accumulating evidence indicates that apnea 
produces high blood pressure in children as young as two years old.  
Extrapolating from findings in adults, children with sleep apnea may be 
predisposed to cerebrovascular, cardiovascular, and infectious/ inflammatory 
diseases.  Sickle cell disease has been associated with sleep apnea in 
children and some reports have linked apnea-induced hypoxemia with sickle 
crises.  Insomnia, hypersomnia, and abnormal function of the body=s internal 
clock (the circadian pacemaker located in the suprachiasmatic nucleus) 
profoundly affects behavioral patterns in children but the neurobiology and 
genetic factors underlying these disorders and their impact on child health 
are not well understood.  Parasomnia type disorders such as sleep terrors, 
enuresis, and bruxism may reflect a developmental process for many children 
that potentially interferes with school performance and aspects of physical 
health.  Children with chronic illnesses such as HIV infection and asthma have 
more difficulty sleeping and may experience higher rates of sleep disturbances 
than the normal population.   Children with sleep disturbances may remain 
untreated because indications for treatment are not well-defined and there is 
a paucity of mechanistic research to support the development of evidence-based 
strategies for diagnosis and treatment. 

Research Scope

This RFA is designed to stimulate basic and clinical research that will 
advance our understanding of (1) the biological, age-specific and ontogenic 
requirements for sleep in healthy children;  (2) pathophysiological mechanisms 
underlying the onset and progression of childhood sleep disorders; and (3) the 
effects of sleep disorders and sleep deprivation on the cardiopulmonary, 
immunological, hematological and behavioral health of children.  Genetic 
control of normal sleep and phenotypic variations in the amount, timing, 
architecture, and electrophysiological characteristics of sleep have been 
reported, but the inter-relationship of these factors on the developmental 
maturation of sleep patterns and circadian rhythmicity, and on the emergence 
of sleep disorders in children needs to be determined.  Listed below are 
examples of studies that would be responsive to this program.  These are only 
illustrative examples and applicants are encouraged to propose  other topics 
consistent with the goals of this program. Not all areas need to be addressed 
in a single application. 

o Elucidate the role of sleep timing and pattern in mechanisms regulating the 
growth and development of healthy children.

o Elucidate the neurobiological and genetic basis of individual variation in 
the sleep response to physical fatigue or sleep deprivation in healthy 

o Elucidate the inter-relationship between sleep and host defense mechanisms 
in healthy children and in children with primary or secondary sleep 

o Elucidate pathophysiological mechanisms linking sleep disturbances in 
children to autonomic, hormonal, immunological, or other abnormalities 
contributing to the development of heart, lung, and blood diseases.

o Elucidate the role of sleep in the acquisition of childhood motor and 
behavioral skills, the control of attention, adaptive coping skills, and the 
developmental integration of new experiences (e.g. procedural learning, 
emotional maturation, and cognitive development).

o Elucidate pathophysiological mechanisms linking sleep disturbances (e.g. 
sleep architecture, habits, and deprivation) in children to mental, 
behavioral, emotional, and cognitive abnormalities as well as changes 
associated with puberty.

o Elucidate neurobiological mechanisms underlying the onset of sleep disorders 
such as narcolepsy, insomnia, and restless legs syndrome in children.  

o Identify biological and genetic factors that affect the susceptibility of 
children to circadian rhythm sleep disorders, especially delayed sleep phase 


In order to be considered responsive to this announcement, applications must 
propose hypothesis-driven studies that focus on biological requirements for 
sleep or the mechanisms linking sleep disturbances to cardiopulmonary, 
immunological, hematological, mental, or behavioral abnormalities in school-
age children.  For the purpose of this RFA, studies must focus on school-age 
children 4 to 18 years of age.   If studies of the inter-relationship between 
chronic disorders and sleep are proposed, the focus must be on mechanisms 
underlying sleep disturbance.  Studies of the circadian system, if proposed, 
must also be tightly coupled to mechanisms of sleep control. Studies proposing 
the use of nonmammalian species or in vitro preparations should clearly 
establish the relationship of these models to the goals set forth in this RFA. 
Collaborations and consortia promoting interdisciplinary approaches between 
scientists studying pediatric sleep disorders, cardiology, pulmonology, 
vascular and sickle cell disease, infectious disease, genetics, 
neurophysiology, endocrinology, immunobiology, and psychology are strongly 
encouraged.  In such cases, each participant's contribution should be 
identified and well-integrated into the overall experimental design.

The elucidation of ethnic, cultural, and environmental factors influencing 
sleep in children, and pharmacological studies focused on investigating the 
efficacy of sleep promoting agents or stimulants to counteract daytime 
somnolence or dyssomnias will not be supported under this RFA.  Studies of 
drug and alcohol abuse, dementia, pain syndromes, anxiety disorders, and the 
disruptive effects of drug therapy on sleep would also be unresponsive to this 
RFA.  Applications focused on the development of methodology, large clinical 
studies, or the establishment of large epidemiological cohorts that collect 
data for future studies are not within the scope of this program.  

Upon initiation of the program, periodic meetings will be organized to 
encourage the exchange of information among investigators who participate in 
this program. Travel funds for a two day meeting each year, most likely to be 
held in Bethesda, Maryland, must be included in the module calculation.  
Applicants must include a statement indicating their willingness to 
participate in these meetings.  Applicants are encouraged to contact the 
program officials listed under INQUIRIES for further information.


It is the policy of the NIH that women and members of minority groups and 
their sub-populations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are provided indicating that inclusion 
is inappropriate with respect to the health of the subjects or the purpose of 
the research. This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects should read the 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 
(; a 
complete copy of the updated Guidelines are available at The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to provide a description of plans 
to conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.


It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by the 
NIH, unless there are scientific and ethical reasons not to include them. This 
policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the Inclusion of Children as Participants in 
Research Involving Human Subjects that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES. Program staff may also provide additional relevant 
information concerning the policy.


All applications and proposals for NIH funding must be self-contained within 
specified page limitations. Unless otherwise specified in an NIH solicitation, 
internet addresses (URLs) should not be used to provide information necessary 
to the review because reviewers are under no obligation to view the Internet 
sites. Reviewers are cautioned that their anonymity may be compromised when 
they directly access an Internet site.


Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of the RFA in 
response to which the application may be submitted. Although a letter of 
intent is not required, is not binding, and does not enter into the review of 
a subsequent application, the information that it contains allows IC staff to 
estimate the potential review workload and plan the review.

The letter of intent is to be sent Dr. Deborah Beebe (see address listed under 
Inquiries below) by September 20, 2001.


The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research and from the Division of Extramural Outreach and 
Information Resources, National Institutes of Health, 6701 Rockledge Drive, 
MSC 7910, Bethesda, MD 20892-7910, telephone 301-710-0267, email:

The modular grant concept establishes specific modules in which direct costs 
may be requested as well as a maximum level for requested budgets. Only 
limited budgetary information is required under this approach.  The 
just-in-time concept allows applicants to submit certain information only when 
there is a possibility for an award. It is anticipated that these changes will 
reduce the administrative burden for the applicants, reviewers and Institute 
staff.  The research grant application form PHS 398 (rev. 4/98) is to be used 
in applying for these grants, with the modifications noted below.



Modular Grant applications will request direct costs in $25,000 modules, up to 
a maximum of ten modules or $250,000 in direct costs per year.  The direct 
costs must be requested in accordance with the program guidelines and the 
modifications made to the standard PHS 398 application  instructions described 

PHS 398

o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in 
$25,000 increments up to a maximum of $250,000) and Total Costs [Modular 
Direct plus Facilities and Administrative  (F&A) costs] for the initial budget 
period.  Items 8a and 8b should be completed indicating the Direct and Total 
Costs for the entire proposed period of support.

of the PHS 398. It is not required and will not be accepted with the 

categorical budget table on Form Page 5 of the PHS 398. It is not required and 
will not be accepted with the application.

o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative 
page. (See for sample 
pages.) At the top of the page, enter the total direct costs requested for 
each year.  This is not a Form page.

o Under Personnel, list all project personnel, including their names, percent 
of effort, and roles on the project. No individual salary information should 
be provided. However, the applicant should use the NIH appropriation language 
salary cap and the NIH policy for graduate student compensation in developing 
the budget request.

For Consortium/Contractual costs, provide an estimate of total costs (direct 
plus facilities and administrative) for each year, each rounded to the nearest 
$1,000. List the individuals/ organizations with whom consortium or 
contractual arrangements have been made, the percent effort of all personnel, 
and the role on the project. Indicate whether the collaborating institution is 
foreign or domestic. The total cost for a consortium/contractual arrangement 
is included in the overall requested modular direct cost amount.  Include the 
Letter of Intent to establish a consortium.

Provide an additional narrative budget justification for any variation in the 
number of modules requested.

o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by  
reviewers in the assessment of each individual's qualifications for a specific 
role in the proposed project, as well as to evaluate the overall 
qualifications of the research team. A biographical sketch is required for all 
key personnel, following the instructions below. No more than three pages may 
be used for each person. A sample biographical sketch may be viewed at:

- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years.
- List selected peer-reviewed publications, with full citations;

o CHECKLIST - This page should be completed and submitted with the 
application. If the F&A rate agreement has been established, indicate the type 
of agreement and the date. All appropriate exclusions must be applied  in the 
calculation of the F&A costs for the initial budget period and all future 
budget years.

o The applicant should provide the name and phone number of the individual to 
contact concerning fiscal and administrative issues if additional information 
is necessary following the initial review. 

The RFA label available in the PHS 398 (rev. 4/98) application form must be 
affixed to the bottom of the face page of the application. Type the RFA number 
on the label. Failure to use this label could result in delayed processing of 
the application such that it may not reach the review committee in time for 
review. In addition, the RFA title and number must be typed on line 2 of the 
face page of the application form and the YES box must be marked.

The sample RFA label available at: has been modified to 
allow for this change. Please note this is in pdf format.

Please note that color figures or photos present in the body of the grant 
application should also be present in the appendix, or high-quality 
reproductions of the pages containing color or half-tone figures should be 
included in the appendix.  The reviewers will receive a black-and-white copy 
of the grant application together with the appendix.

Submit a signed, typewritten original of the application, including the 
Checklist, and three signed, photocopies, in one package to:

BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

At the time of submission, two additional copies of the application as well as 
all five collated sets of Appendix material must be sent to Dr. Deborah Beebe 
at the address listed under Inquiries.  Applications must be received by the 
application receipt date listed in the heading of this RFA. If an application 
is received after that date, it will be returned to the applicant without 

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application. The 
CSR also will not accept any application that is essentially the same as one 
already reviewed. This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must include 
an introduction addressing the previous critique.

Principal investigators should not sent supplementary material without first 
contacting the Scientific Review Administrator (SRA).  The SRA will be 
identified in the letter sent to you indicating that your application has been 
received.  If you have not yet received such a letter, contact, Dr. Deborah 
Beebe at the address listed under Inquiries.


Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NHLBI, NICHD, NIMH, or NINR. Incomplete and/or 
non-responsive applications will be returned to the applicant without further 

Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
the NHLBI in accordance with the review criteria stated below. As part of the 
initial merit review, all applications will receive a written critique and 
undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, 
will be discussed, assigned a priority score, and receive a second level 
review by the NHLBI, NICHD, NIMH, and/or NINR Advisory Council(s). 

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health. In the 
written comments reviewers will be asked to discuss the following aspects of 
the application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals. Each of these 
criteria will be addressed and considered in assigning the overall score, 
weighting them as appropriate for each application. Note that the application 
does not need to be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score. For example, an 
investigator may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

(1) Significance: Does this study address an important problem? If the aims of 
the application are achieved, how will scientific knowledge be advanced? What 
will be the effect of these studies on the concepts or methods that drive this 

(2) Approach: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project? Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

(3) Innovation: Does the project employ novel concepts, approaches or method? 
Are the aims original and innovative? Does the project challenge existing 
paradigms or develop new methodologies or technologies?

(4) Investigator: Is the investigator appropriately trained and well suited to 
carry out this work? Is the work proposed appropriate to the experience level 
of the principal investigator and other researchers (if any)?

(5) Environment: Does the scientific environment in which the work will be 
done contribute to the probability of success? Do the proposed experiments 
take advantage of unique features of the scientific environment or employ 
useful collaborative arrangements? Is there evidence of institutional support?

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research. Plans for the recruitment and retention of subjects will also be 

o The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project 
proposed in the application.


Letter of Intent Receipt Date:    September 20, 2001
Application Receipt Date:         October 16, 2001
Peer Review Date:                 February/March 2002
Council Review:                   May 2002
Earliest Anticipated Start Date:  July 1, 2002


Award criteria that will be used to make award decisions include:

o scientific merit (as determined by peer review)
o availability of funds
o programmatic priorities.


Inquiries concerning this RFA are encouraged. The opportunity to clarify any 
issues or answer questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Michael Twery, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
Rockledge 2, Suite 10018, MSC 7952
Bethesda, MD 20892-7952
Telephone: (301) 435-0202
FAX: (301) 480-3557

Lynne M. Haverkos, M.D., MPH
Child Development and Behavior Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B05B, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 435-6881
FAX: (301) 480-7773
Israel I. Lederhendler, Ph.D.
Coordinator for Sleep Research
National Institute of Mental Health
6001 Executive Boulevard, Room 7-170, MSC 9637
Bethesda, MD  20892-9637 
Tel:  	301/443-1576
Fax: 301/443-4822

Karin F. Helmers, Ph.D.
National Institute of Nursing Research
Building 45, Room 3AN-12
Bethesda, MD 20892-6300
Tel: (301) 594-2177
Fax: (301) 480-8260

Direct inquiries regarding review issues, send letter of intent, and two 
copies of the application to:

Deborah Beebe, Ph.D.
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Dr.,Room 7178 (MSC 7924)
Bethesda, MD 20892-7924

Telephone: (301) 435-0270
Fax: (301) 480-3541

Direct inquiries regarding fiscal matters to:

Robert Vinson
Grants Operations Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7154, MSC 7926
Bethesda, Maryland  20892-7926
Telephone: (301) 435-0171
FAX: (301) 480-3310


This program is described in the Catalog of Federal Domestic Assistance No. 
93.233, 93.242, 93.361, 93.837, 93.838, and 93.839. Awards are made under 
authorization of Sections 301 and 405 of the Public Health Service Act as 
amended (42 USC 241 and 284) and administered under NIH grants policies and 
Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. This program is not 
subject to the intergovernmental review requirements of Executive Order 12372 
or Health Systems Agency review.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and promote the non-use of all tobacco products. In addition, Public 
Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain 
facilities (or in some cases, any portion of a facility) in which regular or 
routine education, library, day care, health care, or early childhood 
development services are provided to children. This is consistent with the PHS 
mission to protect and advance the physical and mental health of the American 

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